Question:

A 28-year-old woman, gravida 2 para 0 abortus 1, at 32 weeks gestation comes to the emergency department because she has not felt her baby move for the past few hours. This pregnancy has been complicated by placenta previa, but she has had no contractions, vaginal bleeding, or leakage of fluid. The patient's other prenatal testing was normal. With her first pregnancy, she had a spontaneous abortion at 8 weeks gestation that required dilation and curettage. The patient's only medical condition is asthma, for which she uses corticosteroid and bronchodilator inhalers. On physical examination, fetal heart tones are not heard with a Doppler device. Transabdominal ultrasound is performed and reveals no fetal cardiac activity, a finding consistent with intrauterine fetal demise. The patient asks how this could have happened to her baby. Which of the following is the most appropriate response?

"Because of your prior miscarriage, this is likely due to a chromosomal abnormality."

"The most common reason is an underlying infection inside the uterus, which could not have been prevented."

"This can sometimes occur as a complication of long-term use of your asthma medications."

"Unfortunately, this is likely a complication of your placenta previa."

"We can order further tests on the baby, but, sadly, we may not ever know the cause."

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Intrauterine fetal demise
Definition	Absent fetal cardiac activity at ≥20 weeks gestation
Risk factors	Aneuploidy Fetal or placental anomalies Fetal growth restriction Congenital infection Substance use (eg, tobacco, cocaine) Maternal conditions (eg, hypertension, diabetes mellitus)
Evaluation	Fetal Autopsy Gross & microscopic examination of placenta & umbilical cord Karyotype/genetic studies Maternal Kleihauer-Betke test Antiphospholipid antibodies Coagulation studies*
Management	20-23 weeks Dilation & evacuation OR vaginal delivery ≥24 weeks Vaginal delivery
Complications	Coagulopathy after several weeks of fetal retention
For history of recurrent pregnancy loss, family or personal history of venous thrombosis, or fetal growth restriction. *Cesarean delivery by maternal choice if history of prior classical cesarean/myomectomy.

Intrauterine fetal demise (IUFD), or stillbirth, refers to fetal death at ≥20 weeks gestation and prior to delivery. Patients often have decreased or absent fetal movement. On evaluation, no fetal heart tones are audible on Doppler sonography, and ultrasonography visually confirms the absence of fetal cardiac activity.

The pathophysiology of IUFD can be maternal, fetal, or placental in origin. Therefore, evaluation includes the following:

Fetal autopsy and karyotyping or genetic studies
Gross and microscopic evaluation of the placenta for thrombosis, abruption, infection, or other disease
Maternal laboratory testing for antiphospholipid syndrome and fetomaternal hemorrhage
Other testing (eg, evaluation for thrombophilia, cultures) to confirm or exclude other etiologies based on the patient's medical history

Identifying a possible cause not only provides patients with an answer, but also helps determine the recurrence risk and optimal management of future pregnancies. Even after thorough evaluation, up to half of IUFDs have no identifiable cause. Therefore, patients should be counseled in advance that testing may be negative.

(Choice A) Chromosomal abnormalities are common causes of first-trimester spontaneous abortions. However, at ≥20 weeks gestation, genetic abnormalities typically cause anomalies (eg, cardiac defect) that are visible during ultrasonography. This patient's ultrasounds were normal, making a genetic defect less likely.

(Choice B) Infections (eg, parvovirus, syphilis, cytomegalovirus, Listeria monocytogenes) can cause preterm IUFD. However, they are usually associated with maternal symptoms (eg, fever, malaise) or abnormal fetal ultrasound results, making this diagnosis less likely.

(Choice C) Some medications (eg, ACE inhibitors, lithium) are teratogens and cause congenital anomalies; other substances (eg, cocaine) can cause placental abruption, obstetric hemorrhage, and IUFD. However, corticosteroid and bronchodilator inhalers are not associated with IUFD.

(Choice D) Placenta previa, the implantation of the placenta over the internal os, increases the risk for placental injury and bleeding that can lead to IUFD. However, patients typically have vaginal bleeding, which is not seen in this patient.

Educational objective:
Intrauterine fetal demise refers to fetal death at ≥20 weeks gestation and prior to delivery. The etiology can be maternal, placental, or fetal in origin, but, most often, the cause is unknown.